Controlled adjustment of the respiratory gases has allowed extension of manned activity to extreme altitude, to the lunar surface, and to deep undersea regions. This program concerns the circumstances in which natural or other respiratory gases effect such functional states in health as well as in disease. It includes determination of the ultimate limits of tolerance to unusual environments. Metabolically active and inert respiratory gases are studied by dose-response methods to elaborate limits of tolerance. Adaptions and deteriorations of sensory, cognitive, neuromuscular, pulmonary, respiratory, cardiovascular and exercise functions are determined. Investigation of inert gas exchange in organs and tissues provides the basis for systems of decompression and understanding of factors in bubble formation and resolution. In addition to abnormal environments, interrelated studies are therefore concerned with respiratory, cardiovascular, gas transport and metabolic influences of both low and high oxygen pressures in disease. Investigation concerns oxygenation, oxygen toxicity and extension of oxygen tolerance in therapeutic and in other uses of hyperoxygenation, as in diving.